This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESCRIPTION Overview: Jain (PI) This Center of Biomedical Research Excellence (COBRE) at the UD aims at developing structural and recognition motifs that control functions of macromolecules and are useful for design of biomaterials. These encompass atomic-level interactions among small molecules to proteins to mesoscale assemblies. Design paradigms are being developed for the study of small molecule-protein interactions, protein assembly in membrane environments, the construction of artificial glycoprotein scaffolds to display multivalent recognition motifs, and the preparation of peptide-based biomaterials whose structures and functions are responsive to environmental cues. Synthetic methods are being pursued to prepare non-natural amino acids for incorporation into proteins to impart unique structure and function. Five projects are being carried out to incorporate both fundamental and applied research components. All of these projects require detailed information about the interplay of structural motifs. These motifs range from characteristic macromolecular surfaces, domains, and scaffolds to the functionally significant of specific amino acid side chain residues. Importantly, design principles established within each individual project can be applied across all of the projects to enhance current design strategies and further the general understanding of biomolecular recognition. All the projects are under the individual supervision of Assistant Professors in the Department of Chemistry and Biochemistry (DCB) and the Department of Materials Science and Engineering (MSEG). Broadly speaking, projects 1, 3 5 and 6 (new project with Dr. Polenova) are in the area of structural biology, and 2 and 4 are in bioengineering through materials. Project 3 complements these two general areas by developing novel synthetic methodology for the preparation of non-natural amino acids that will elicit new protein structural and functional features. Importantly, the proposed Center will serve to integrate the newly established Materials Science and Engineering Department and the Organic division of the Chemistry and Biochemistry Department into biomedical-related research directives within the University. A seventh project on Computational Chemistry of Macromolecules will be initiated in September 2006 with the recent hire of Dr. Sandeep Patel and the departure of Dr. Clifford Robinson. In addition, this Center will strongly complement not only the Protein Structure Initiative (PSI) launched by the National Institutes of Health (NIH), but also other biomedical research efforts on campus and surrounding institutions. Core facilities to be provided, as part of this COBRE will enhance those currently being established on campus and serve to strengthen all of the biomedical research efforts at the UD.